Our research objective is to investigate the possibility of protecting experimental animals against tumors induced by polycyclic aromatic hydrocarbon (PAH) carcinogens by immunizing them with non-carcinogenic analogs of these carcinogens. Recently, we have obtained direct evidence favoring this possibility. Guinea pigs and mice immunized with 5-fluoro-12-methylbenzanthryl-7-acetic acid (5-FMBAAA) conjugated to bovine serum albumin (BSA) develop antibodies capable of binding a spectrum of carcinogenic PAH's. When we immunized CD-1 mice with the 5-FMBAAA-BSA conjugates, they developed significantly fewer skin tumors in response to low doses of the carcinogen dimethylbenzanthracene (DMBA) than did control mice. Our current aims include a determination of the scope of this protection in CD-1 mice by testing a range of DMBA doses (all in conjunction with the tumor promoter, phorbol myristate acetate); in addition, protection will be tested in skin cancer sensitive (Sencar) mice. We also wish to determine whether, in addition to antibodies, cell-mediated immune reactions contribute to protection against tumors. Cell-mediated immunity to DMBA in 5-FMBAAA-BSA-immunized mice will be measured by an ear-thickness technique, and the ability of cell-mediated immune reactions to an unrelated antigen, oxazolone, to affect tumor incidence in the skin of mice undergoing DMBA carcinogenesis will be investigated. A possible role for metabolic alterations in protection will be examined by studying the effect of 5-FMBAAA on the PAH-metabolizing enzyme system, aryl hydrocarbon hydroxylase. To extend the range of feasible protection studies, we will attempt also to prepare "hybridomas" which will produce pure antibodies against DMBA in large quantities. Spleen cells from mice immunized with 5-FMBAAA-BSA conjugates will be fused with NS-1 mouse myeloma cells, and the resulting hybridomas will be examined for DMBA-binding antibodies. Finally, as a prototype of the use of protection against specific carcinogens as an epidemiologic probe capable of determining the role of those carcinogens in the causation of naturally occurring tumors, the effect of 5-FMBAAA-BSA immunization on spontaneous tumor incidence in mice will be determined.